Activation of blood components such as lymphocytes, granulocytes, monocytes, and platelets is associated with the release of thromboxane A.sub.2 and other metabolites of arachidonic acid. Thromboxane A.sub.2 (TXA.sub.2) is formed from metabolism of arachidonic acid by the enzyme cyclooxygenase via cyclic endoperoxide intermediates. TXA.sub.2, the major cyclooxygenase product in the platelet, is a vasoconstrictor and potent stimulus to platelet aggregation in vitro.
Platelets express a high synthetic capacity for thromboxane A.sub.2 (TXA.sub.2) and therefore this product may have clinical diagnostic significance. However, TXA.sub.2 itself is chemically unstable with a half life of less than one minute. For this reason the stable breakdown product thromboxane B.sub.2 (TXB.sub.2) and its primary metabolite 2,3 dinor-TXB.sub.2 are usually measured by RIA when large numbers of samples are required.
FitzGerald et al., "Analysis of Prostacyclin and Thromboxane Biosynthesis in Cardiovascular Disease," Circulation 67(6):1174 (1983) focuses on the methods that have been used for measuring prostacyclin and thromboxane A.sub.2 in human biological fluids. After reviewing the difficulties associated with invasive analysis techniques for measuring prostacyclin and thromboxane A.sub.2, the authors assert that the measurement of urinary metabolites represents the only noninvasive approach to quantitation of endogenous prostacyclin and thromboxane A.sub.2 biosynthesis. In conclusion, the report states that further research is needed to define the relationship of tissue-specific, capacity-related indexes to endogenous production rates of prostacyclin and thromboxane A.sub.2.
In thrombotic events such as deep vein thrombosis (Foegh et al., "Urine i-TXB.sub.2 in Renal Allograft Rejection," Lancet II:431-434 (1981)) and pulmonary embolism (Klotz et al.. "Urinary Excretion of Thromboxane B.sub.2 in Patients with Venous Thromboembolic Disease," Chest 85:329-335 (1984)), and in renal and cardiac transplant rejection (Foegh et al.. "Lipid Mediators in Organ Transplantation," Transplant. Proc. 18, suppl. 4: (1986)), the urinary excretion of immunoreactive-TXB.sub.2 (i-TXB.sub.2) which includes 2,3 dinor TXB.sub.2, is significantly increased.
For illustration, in Foegh et al., Lancet, supra report that not only may urinary i-TXB.sub.2 be a predictor of clinical renal allograft rejection, it may also be a used in the early diagnosis of venous thrombosis. Klotz et al., Chest, supra, studied the use of urinary i-TXB.sub.2 as an indication of platelet activation and as a possible adjunct for diagnosing acute thromboembolic disease.
Coronary artery thrombosis, which may lead to acute myocardial infarction, is another thrombotic event where an increase in thromboxane formation might be anticipated. Attempts to measure plasma values are not entirely satisfactory owing to the large potential for sampling artefacts. (Granstrom et al., "The Thromboxanes," in Prostaglandins and Related Substances, (C. Pace-Asciak and E. Granstrom eds.), Elsevier, Amsterdam (1983), p. 45) Urinary i-TXB.sub.2 determinations provides a means of avoiding such artefacts but whether infarction is associated with a rise in urinary i-TXB.sub.2 is not known.